This proposal is a competitive renewal for an investigator-initiated, randomize, double-blind, multicenter, clinical trial currently testing the primary null hypothesis that, up to two years, warfarin and aspirin therapy will not differ in the frequency of death or ischemic stroke recurrence. Secondary null hypotheses are that warfarin and aspirin therapy will not differ in frequency of death or ischemic stroke recurrence over one year; that the effect of warfarin therapy, compared to aspirin, on death or stroke recurrence, will not be modified by baseline stroke severity, baseline stroke subtype, baseline lesion size, location of baseline infarct, ethnicity, gender, and age; and that warfarin and aspirin therapy will not differ in frequency of complications. Aspirin 325 mg daily is the platelet antiaggregant. Warfarin dose is adjusted to keep the INR at 1.4 to 2.8. Patients with ischemic stroke due to cardiac embolism or treated by endarterectomy are ineligible. Patients are randomized within 30 days after stroke and treated for up to two years, followed monthly by phone and quarterly in person to regulate the hematologic effects of medication and to detect the primary endpoints of death and symptomatic stroke recurrence, and to detect complications of therapy. To maintain blinding, the laboratory data are sent to the Data Management Center. PT/INR results sent to the local centers are correct for patients on active warfarin but are falsified for those on aspirin. An emergency notification system helps maintain patient safety. Through 24-Oct-1996 1603 patients have been recruited from 49 participating centers toward the 1,920 patient sample size.